Reticuloendotheliosis virus (REV) is an avian oncornavirus. Unlike other C-type viruses, it is highly virulent: its incubation period may be as short as 4 days, and mortality approaches 100%. It is the prototype of a recently proposed group which now includes three other viruses. The objectives of the proposal are four-fold. We have recently isolated transformed bone marrow lines which produce infectious REV. REV does not transform chick embryo fibroblast cultures, and the virus produced by them is attenuated. We would like to define the basis for the attenuation of CEF-REV. Three possible explanations are that CEF cultures select against an essential helper, that envelope glycoproteins are altered, or that CEF-REV contains an inadequate level of DNA polymerase. The second objective involves the investigation of the replication of REV in vitro. We will examine the synthesis and cellular location of virus-directed proteins, employing combined immunological and cell fractionation techniques. The third objective is to determine whether REV and the other viruses in the group, which have been isolated from three avian species, have a common group-specific antigen. Antiserum prepared against the major internal proteins of REV should be of value in confirming the membership of the group and in identifying new members. The fourth objective is to investigate the involvement of various cell types and the interactions of the immune system in the development of this rapidly lethal neoplastic disease.